Reaction of alkylphenol, tertiary amine, and epihalohydrin



Patented Apr. 10, 1951 UNITED OFFICE John F. Olin, Grosse Ile, Mich.,assignor to Sharples Chemicals Inc., a corporation of Delaware NoDrawing. Application June 23, 1948, Serial No. 34,811

12 Claims. 1

This invention pertains to a new process for producing compounds havingthe formula:

wherein R represents an alkyl radical having from to 18 carbon atoms;wherein X represents halogen, that is, chlorine, bromine, iodine orfluorine; wherein R1 represents an alkyl radical having from 1 to 3carbon atoms; wherein R2 represents an alkyl radical having from 1 to 3carbon atoms; wherein R3 represents one of the group consisting of theallyl radical, the benzyl radical and alkyl radicals having from 1 to 3carbon atoms.

I have discovered that compounds coming within the scope of theabove-mentioned formula have outstanding properties when used as surfaceactive agents or bactericides, and that these properties are imparted tothese new compounds by the particular molecular structure thereof.

When these compounds are to be employed primarily as surface activeagents, as, for example in textile'treating baths, I prefer those inwhich the alkyl radical represented by R contains from 8 to 16 carbonatoms and in which the radicals represented by R1, R2 and R3, takenindividually, are selected from the group consisting of methyl and ethylradicals.

7 On the other hand, when these compounds are to be employed primarilyas bactericides, I prefer those in which the alkyl radical R containsfrom 6 to 12 carbon atoms, in which the radicals represented by R1 andR2 are selected from the group consisting of methyl and ethyl radicals,and in which the radical represented by R3 is selected from the groupconsisting of the allyl radical and the benzyl radical.

In the production of these compounds, I bring together eithersimultaneously or in any desired order of addition, three reactants asfollows:

1. A phenol having the formula wherein R represents and alkyl radicalhaving from 5 to 18 carbon atoms.

2. Epihalohydrin, for example, epichlorhydrin or epibromohydrin.

3. A tertiary amine having the formula wherein R1 represents an alkylradical having from 1 to 3 carbon atoms; wherein R2 represents an alkylradical having from 1 to 3 carbonatoms; wherein R3 represents a radicalselected from the group consisting of the allyl radical, the benzylradical and alkyl radicals having from 1 to 3 carbon atoms.

In order that the reaction may proceed at a reasonable rate, I prefer tohave the reaction take place at a temperature above 20 C., and in orderto limit the percentage of by-products produced, I prefer to havereaction take place at a temperature below 120 0. However, it is to beunderstood that, if desired for any reason, the temperature of thereaction mixture may be taken above or below the range of from 20 C. to120 C. such as for a part of the reaction period without departing from/the spirit of the invention, and bearing in mind that a reducedtemperature will slow up the reaction and that an elevated temperatureis likely to result in the production of considerable quantities ofundesired by-products. Particularly excellent results may be attained byconducting at least the major portion of the reaction while maintainingthe temperature of the reaction mixture within the range of from 50 C.to C.

Any convenient or desirable expedient may be employed for maintainingthe temperature of the reaction within the desired range, such as, theuse of a jacketed reaction vessel, or the use of heat exchange coilswithin the reaction mixture, or otherwise.

The reaction is carried out in liquid phase with or without the presenceof a solvent or diluent which is inert to the reaction under theconditions obtaining, the presence of a solvent in any suitable ordesired quantity being preferred in many instances. Thus, I frequentlyprefer to use from 25 to by volume of solvent based on the volume ofreactants employed.

Although in general any non-reacting solvent or diluent may be employedsuch as an aromatic hydrocarbon, an aliphatic hydrocarbon or an ether, Ihave found that very satisfactory results are obtained by use, as asolvent, of a lower saturated aliphatic monohydric alcohol, i, e. analkanol. Among the alcohols which may be so employed, for example, aremethanol,. ethanol,

3 propanol, butanol, pentanol and hexanol, including the variousisomeric forms thereof.

Obviously any suitable pressure may be employed, such as atmospheric,subatmospheric or superatmospheric, while causing the reaction to takeplace in the liquid phase. In many instances it is convenient to employa solvent which boils at or near the desired reaction temperature underthe pressure conditions obtaining, and to maintain a reflux of saidsolvent, thereby causing a uniform temperature to be maintained in thereaction mixture. Isopropanol serves admirably for this purpose whenoperating near atmospheric pressure.

While all of the reactants may be combined simultaneously, I find itexpedient for purposes of heat control, the reaction being exothermic,to first mix a part or all of the phenol with :a part or all of theamine, and then to add the epihalohydrin, for instance, epichlorhydrin,gradually to the foregoing mixture. If only a part of the phenol or ofthe amine or both were initially combined, the remainder may be addedgradually, or in increments, or in a body, as the reaction proceeds.

For instance, a part of the amine may be added to the phenol followed bythe addition of the epihalohydrin gradually or in increments, or as abody if proper heat control facilities are avail able, and after all orpart of the epihalohydrin has been combined, the remainder of the aminemay be added to the reaction mixture. Thus, for example, from 1 to ormore of the amine may be added to the phenol, followed by the additionof the epihalohydrin, and then the remainder of the amine may be added.

Any other order of addition may be resorted to.

My process fundamentally involves the chemicaltcombination of thephenol, the epihalohydrin and the tertiary amine in stoichiometricproportions to form the corresponding quaternary salt, and the reactionmay :be conducted by use of the three reactants in substantiallystoichiometric amounts. It will be understood, however, that thereactants maybe employed in any other desired ratios during thereaction, and the .excess maysubsequently be removed by any suitablemeans. As a general rule, I prefer to have all or part' of the alkylphenol present whenever the amine is mixed with the epihalohydrin,

While the foregoing"contemplates more particularly addition of thereactants on the batch principle, it includes within its purview opera-3 tions on the continuous, semi-continuous or other principle, wherebythe three reactants are brought together for reaction purposes Whilepreferably maintaining the temperature of the reaction mixture betweenC. and 120 C.

While .I do not wishto be bound by any theory as to the manner inwhichthe reaction proceeds, the amine in addition to reacting to formthe desired quaternary ammonium compound apparently also catalyzes .thereaction between the phenol and the epihalohydrin, since it is un-:necessary to add to the reaction any other compound in order for thereaction to-proceed. While the invention does not preclude the additionof any other compound forpurposes of assisting the reaction, "as abovepointed out, such addition is unnecessary for my purposes.

Thus, any such other catalyst .may be added, ifgdesired. It ispreferred, however, that any such additionshould not interfere with thereaction, or result in the production of by-products 'inundesiredquantities.

Suitable catalyst for the condensation of the epihalohydrin with thephenol in practice of my invention are, in addition to the tertiaryamines employed in the reaction, those organic catalysts for thecondensation of phenols with epoxides which are neutral or basic inreaction and which contain chemically bound nitrogen. Epoxidecondensation catalysts of this character, including, for example,primary amines such as monoalkyl amines having from 1 to 5 carbon atomsin the alkyl radical, for instance, monobutyl amine, secondary aminessuch as dialkyl amines having from 1 to 5 carbon atoms in each alkylradical, for instance, dibutyl amine, tertiary amines (which may beeither aliphatic, aliphatic-aromatic, or aromatic in character) such asthe tertiary amines employed as reactants herein, as well as alkyl-arylamines and aryl amines such as dimethyl aniline and triphenyl amine,amine oxides such s trialkyl amine-oxides having from 1 to 5 carbonatomsin each alkyl radical, for instance, triethyl amine oxide,hexamethylene tetramine, urea, substituted ureas such as the alkyl ureashaving from 1 to 5 carbon atoms in each alkyl radical of which there maybe from 1 to 4 attached to the nitrogen atoms, for instance, tetraethylurea, guanidine, substituted guanidines, such as the alkyl guanidineshaving from 1 to 5 carbon atoms in each alkyl'radical of which there maybe from 1 to 4 attachedto the nitrogen atoms of the amine groups,such'a's symmetrical dibut'yl guanidine, etc., are capable of promotingcondensation of the alkyl phenol with the epihalohydrin to formcondensation products which may readily be converted in high yield intomy quaternary ammonium salts by reaction with the appropriate tertiaryamines. When practicing my invention by use of organic,nitrogen-containing, epoxide-condensation catalysts other than thetertiary amine to be-quaternized, I prefer to employ the catalyst :inrelatively small proportion, say from to 5 per cent by weight based onthe phenol, in order to minimize the contamination of the ultimateproduct.

However, the procedure more particularly de-- scribed herein ispreferred, and results in greatly improved yields and quality of productExamples of phenols suitable for use in the practice of my invention areas follows:

The amyl phenols, such 'as, normal amyl phenol, secondary amyl phenoland tertiary amylphenol, in which said al-kyl radicals may be attachedin the ortho, the meta or the para position; and thecorresponding hexyl,heptyl, octyl, nonyl, deoyl, undecyl, 'dodecyl, tridecyl, tetradecyl,'pentadecyl, hexadecyl, heptadecyl and octadecyl phenols.

It is not necessary in practice of 'my invention that the phenolemployed be a relatively pure compound, and in many instances it may bedesirable or expedient to employ a homologous or an isomeric mixture ofphenols, or both.

Tertiary alkyl phenols are preferred, particularly when the tertiaryalkyl radical is derived from an open chain polymer olefin resultingfrom the polymerization of an open chain olefin of lower carbon content,such as propylene, butene-l, butene-2, isobutene, any of the isomericpentenes, any of the isomeric hexenes, or of mix- ;turesof two or moreof "the foregoing.

Methods of polymerizing ol'efins of lower car"- bon content to "formpolymer olefins of higher carbon content are well known in the art, asare methods for the alkylation of benzene ring comg. pounds, includingphenols, employing such poly mer olefins as the source of the alkylradicals.

Some examples of amines which may be quaternized in the practice of myinvention are as follows:

Trimethylamine, triethylamine, trinormalpropylamine, dimethylethylamine,methyldiethylamine, dimethylbenzylamine, diethylbenzylamine,dimethylallylamine, diethylallylamine, methylethylallylamine, andmixtures thereof.

My preferred process has outstanding advantages in that the highlydesirable quaternary compounds of my invention may be prepared inexcellent yield and quality, from available and relatively inexpensiveraw materials, by a simple method and with the use of conventionalequipment. In addition the reaction may take place. if desired, in asingle vessel, and without necessitating the separation of intermediatereaction products or intermediate by-products, such as catalystresidues, unused catalysts, etc.

The reaction proceeds smoothly and fairly rapidly.

Further features of the invention are illustrated in examples asfollows:

EXAMPLE 1 3-(p-tert dodecylphenoxy) 2 hydroxypropyltriethylammoniumchloride 384 grams (1.5 moles of p-tertiary-dodecyl phenol and 152 grams(1.5 moles) triethylamine were placed in a reaction flask, equipped witha reflux condenser, together with 200 grams of isopropanol as solventand the mixture was brought to reflux temperature. 139 grams (1.5 moles)of epichlorhydrin was introduced and the reaction mixture was refluxedfor sixteen hours. For purposes of purification, the crude product wasthen diluted with 1500 ml. of water to give a clear solution. Theaqueous solution was treatedwith sufiicient toluene (3 liters) to causeseparation of an oil layer of about 1 liter. The separated oil layer wasdiscarded and the aqueous layer was again washed with about 1500 ml. oftoluene and was subjected to a flash-evaporation procedure EXAIWPLE 2 3-(p-tert octadecylphenomy) 2 hydroprop'yltriethylammonium chloride By theprocedure of Example 1, 346 grams (1 mole) of tertiary octadecyl phenol,prepared by alkylation of phenol with propylene hexamer, 92.5 grams (1mole) of epichlorhydrin and 101 grams (1 mole) of triethylamine werereacted for thirty hours in isopropanol solution. It was observed that93% of the amine had reacted at the end of twenty hours and that theadditional ten hours of reaction efiected substantially no furtherconversion. -After purification the product was obtained 'in'an amountcorresponding to 85% yield. Its surface activity and detergency as shownby standard tests was slightly lower than in the case of thecorresponding compound derived from tertiary dodecyl phenol. it possessed great emulsifying power.

EXAMPLE 3 3-(p tert-octadecylphenoxy) -2-hydroxypropyltrimethylammom'umchloride 692 grams (2 moles) of tertiary octadecyl phenol was reactedwith 185 grams (2 moles) of epichlorhydrin and trimethylamine in thepresence of isopropanol in the following manner.

' The phenol and the solvent were placed in a flask and thetrimethylamine was introduced at a slow uniform rate below the surfaceof the reaction mixture, the latter being maintained at about C.throughout the reaction period. Any amine which escaped from thereaction system was recondensed in a suitable reservoir and wasreintroduced into the system. thus providing a uniform flow of aminethrough the reaction vessel. The epichlorhydrin was added dropwise overa period of fifty minutes, and circulation of the trimethylamine wascontinued for five hours at the end of which period approximately thetheoretical quantity of the amine (2 moles) had been consumed in thereaction. After extraction of minor amounts of impurities the productwas concentrated and taken up in diluted alcohol. Its dilute aqueoussolutions foamed strongly and were efiicient washing agents andgermicides.

EXAMPLE 4 3- (tert-nonylphenoxy) -2-hydromypropyltriethylammoniumchloride A mixture of 280 grams (1.27 moles) of tertiary nonyl phenol,200 grams of anhydrous ethyl alcohol and 3 grams of triethylamine wasbrought to reflux temperature and 120 grams (1.30 moles) ofepichlorhydrin was introduced over a twenty minute period. The mixturewas refluxed for an additional two hours resulting in condensation ofapproximately 50% of the phenol with the epichlorhydrin. 138 grams (1.39moles) of triethylamine was then introduced and refluxing was continued.After 3.5 hours, 0.41 equivalent of amine remained unreacted. Aftersixteen hours, when the reaction was discontinued, all but 0.124equivalent of the amine had been consumed. The product was isolated ingood yield and proved to be a highly effective wetting agent and wooldetergent and a moderately effective germicide. It was furthermore foundthat its surface activity could be extended (i. e., it could be built)by incorporating substantial prop'ortions'of inorganic salts such assodium sulfate or sodium pyrophosphate.

EXAMPLE 5 3- (undecylphenoxy) -2-hydro:1:ypropyltrieth:1ll-

' ammonium chloride 744 grams (3.0 moles) of a mixed monoalkyl phenolhaving an alkyl group averaging 11 carbon atoms, 450 grams of solventnaphtha and 12 grams of triethylamine oxide were mixed and held atreflux temperature during gradual addition of 291 grams (3.14 moles) ofepichlorhydrin. Reflux temperature was maintained for an additional 2.5hours after which 3.30 moles of triethylamine were introduced, themixture being then further reacted for twenty hours. Purification inthis instance was accomplished by passing steam at C. through theviscous product contained in a stainless steel mixer which was operatedto provide sufiicient heat and vacuum to prevent condensation of thesteam and suflii the temperature.

cient agitation of the product to effect intimate contactin with thesteam. The desired quaternary salt was thereby obtained in high purityin 78% yield. 7

' EXAMPLE 6 3- (p-tert-nonylphenomy)-2-hydromypropyldimeihylbe'neyZammonium chloride 400 grams (1.82 moles)of nonyl phenol derived by the alkylation of phenol with propylenetrimer, 300 grams of isopropanol and 10 ml. of dimethylbenzylamine werebrought to reflux and 168 grams (1.82 moles) of epichlorhydrin was addedover a period of one hour. Refluxing was continued for five hours.Another 300 grams of isopropanol and the remainder of 246 grams (1.8-2moles) of the dimethylbenzylamine was introduced. This mixture wasrefluxed for twenty hours. Titration showed that only .03 equivalent offree amine remained. 1200 ml. of toluene was added and the mixture wasthen extracted once with 500 m1. and twice with 300 ml. of water.

The toluene layer was evaporated to 705 grams and was diluted with 800ml. of isopropanol and 3200 ml. of water. The combined aqueous solutionswere then extracted with three portions of hexane to provide an aqueouslayer containing 745 grams of the desired quaternary salt.

EXAMPLE '7 3- (p-tert-octylphenory)-2--hydr0:cypropyldimethylbenzylammonium chloride A mixture consistingof 2 moles of epichlorhydrin, l-mole of p-tert-octylphenol, 7 grams ofdimethylaniline and 200 cc. of isopropyl alcohol was refluxed atatmospheric pressure for sixteen hours. The solvent, together with theexcess epichlorhydrin, was then vaporized out of the reaction mixture byapplication of a temperature of 100 C. and a pressure of 25 mm.absolute. The residual condensation product was quaternized with 1 moleof dimethylben-zylamine by re nursing the mixture for two hours inmethanol solution; Naphtha-was then added and the mixture was distilledthrough a column until the overhead temperature reached 90 C. to effectremoval of methanol. About 50 cc. of water was added to the residue atabout 60 Chatter which crystallization was induced by further reducingThe precipitate, which was segregated by filtration, washed with waterand dried at a moderate temperature, was a white crystalline monohydrateof the desired quaternary salt. It melted at 110 C. and was found uponanalysis to contain 7.8% ionizable chlorine and 3.1% nitrogen "ascompared with corresponding theoretical values of 7.8% and 29%respectively. The melting point of the anhydrous product wasapproximatelyV162-164 C.

The following example illustrates "an alterna: tive method for, thepreparation of my com-'- u 3- (tert-no nylpl zenomy)-2-hydro:cypropyZdicrhQ/Z- ben'eylammom'um chloride 220 parts ofnonylphenol were reacted with 92.5 parts of ep-ichlorhydrin in 200 partsof isopropanol with parts of dimethylaniline as catalyst by refluxingfor four hours. This product was then reacted with 146 parts ofdiethylamine by adding the diethylamine to the above solu- P29 and efl xn r 1.20. hams ri ra en 8. showed the reaction to have proceeded 98%..200 cc. of 10 normal sodium hydroxide was added and the organic layerwhich formed was separated and washed twice with water. This product wasthen steamed and dried. The final product had a neutral equivalent of34'? (calculatedv 349) 174 parts of the above product, 63.5 parts ofbenzyl chloride and 100 parts of isopropanol were refluxed together for20 hours. Water was then added to the reaction mixture slowly until afaint 'tubidity developed. An additional amount of water "was addedslowly (about 10 cc.) until 25 grams of oil had separated. The oil wasdiscarded. The remaining solution contained the desired quaternarysubstantially free from unreacted reagents. The desired quaternary wasobtained by evaporating the solvent. .Itwas a very viscous amber liquid,only slightly soluble in water.

Examples of other quaternary salts which have been prepared inaccordance with the process of my invention include:

3 (t amylphenoxy) 2 hydroxypropylbenzyldimethyl ammonium chloride 3 (toctylphenoxy) 2 hydroxypropyldimethylallyl ammonium chloride 3 (toctylphenoxy) 2 hydroxypropyldi ethylbenzyl ammonium chloride 3 (sdecylphenoxy) 2 hydroxypropyltripropylammonium chloride 3 (ndodecylphenoxy) 2 hydroxypropyltrimethyl ammonium bromide 3 -.(thexadecylphenoxy) e 2 'hydroxypropyldimethylethyl ammonium chloride Theforegoing examples are merely illustrative of various embodiments of myinvention and I do not wish to be limited except by the scope of thefollowing claims.

I claim:

1. A process comprising mixing in liquid phase and under temperatureconditions between 20 C. and C. a monoalkyl phenol having from 5 to 18carbon atoms in the alkyl radical, an epihalohydrin, and a tertiaryamine having the formula:

in which each of R1 and R2 is an alkyl radical having from 1 to 3 carbonatoms, and in which R: is one of a group consisting of the allylradical, the benzyl radical and alkyl radicals having from 1 to 3 carbonatoms; and maintaining the foregoing in mutual contact forstoichiometric reaction until the corresponding quaternary ammoniumreaction product is obtained.

'2. The process of claim 1 in which the reaction is carried out in thepresence of a solvent which is inertto the reaction.

3. The process of claim 2 in which the solvent is an alkanol containing.from 1 to 6 carbon atoms.

{1. A process comprising mixing in liquid phase and under temperatureconditions between 20 C. and 120 C. a monoalkyl phenol having from 5 to18 carbon atoms in the alkyl radical, epichlorhydrin, and a tertiaryalkyl amine having from 1 to 3 carbon atoms in each alkyl radical, andmaintaining the foregoing in mutual contact for stoichiometric reactionuntil the corresponding quaternary ammonium reaction prod- 7 u tisetame- 5.. The process of claim 4 in a tertiary alkyl phenol.

6. A process comprising mixing in liquid phase and under temperatureconditions between 20 C. and 120 C. a monoalkyl phenol having from 5 to18 carbon atoms in the alkyl radical, epichlorhydrin, and a monoallyldialkyl amine hav- I ing .from 1 to 3 carbon atoms in each alkylradical, and maintaining the foregoing in mutual contact forstoichiometric reaction until the corresponding quaternary ammoniumreaction prod- 9. A process comprising mixing in liquid phase which thephenol is and under temperature conditions between 20 i0 respondingquaternary ammonium reaction product is obtained.

10. The process of claim 9 in which the phenol is tertiary alkyl phenol.v p

11. The process of c1aim'9-in which the phenol is tertiary octyl phenol,and the amine is dimethylbenzyl amine.

12. The process of claim 9 in which the phenol is tertiary octyl phenol,and the amine is "diethylbenzyl amine.

JOHN F. OLIN.

REFERENCES CITED The following references are of record in the file ofthis patent:

UNITED STATES PATENTS

1. A PROCESS COMPRISING MIXING IN LIQUID PHASE AND UNDER TEMPERATURECONDITIONS BETWEEN 20* C. AND 120* C. A MONOALKYL PHENOL HAVING FROM 5TO 18 CARBON ATOMS IN THE ALKYL RADICAL, AN EPIHALOHYDRIN, AND ATERTIARY AMINE HAVING THE FORMULA: